Some standard content:
GB 17787 .-1999
This standard adopts the quality control items, test methods and indicators of the product in the 23rd edition of the United States Pharmacopoeia (1995) and refers to the Appendix of Part II of the 1995 edition of the Pharmacopoeia of the People's Republic of China. According to the production process of my country and the quality analysis results of multiple batches of products, three control indicators of appearance, residual acetone and cyanide are added, the control item of potassium is deleted, the identification method is changed from infrared method to chemical method, and the content determination method is improved. The improved method is fast, simple, economical, easy to determine the endpoint, high accuracy and good precision. After comparing the results of the same batch of samples with the content determination method of the product in the 23rd edition of the United States Pharmacopoeia (1995), the results are consistent. The determination of heavy metals and arsenic adopts the general method of food additives in my country, and the determination of sodium, cyanide, chloride and ash is carried out in accordance with the provisions of the Appendix of Part II of the 1995 edition of the Pharmacopoeia of the People's Republic of China.
This standard is proposed by the State Food and Drug Administration. This standard was drafted by China Pharmaceutical Industry Corporation. This standard is under the jurisdiction of Tianjin Pharmaceutical Research Institute. This standard was drafted by Northeast Pharmaceutical Factory. The main drafters of this standard are Li Yuchen, Li Zhongmei, Zhang Yanqiu, Shao Ping and Zhang Haiyan. 312
1 Scope
National Standard of the People's Republic of China
L-carnitine
Food additive
Levocarnitine
GB17787-1999
This standard specifies the requirements, test methods, inspection rules, marking, packaging, transportation and storage requirements for the food additive L-carnitine. This standard applies to L-carnitine prepared with epichlorohydrin as the starting material, which can be added to food as a nutritional enhancer. 2 Referenced Standards
The provisions contained in the following standards constitute the provisions of this standard through reference in this standard. When this standard is published, the versions shown are valid. All standards will be revised. Parties using this standard should explore the possibility of using the latest versions of the following standards. GB/T8450—1987 Determination of arsenic in food additives GB/T8451-1987 Test method for heavy metal limits in food additives Part II of the 1995 edition of the Pharmacopoeia of the People's Republic of China (Chinese Pharmacopoeia for short) 3 Chemical name, structural formula, molecular formula, relative molecular mass Chemical name: (R)-3-Carboxy-2-hydroxy-N,N,N-trimethyl-1-propylamine hydroxide inner salt (R) -3-Carboxy-2-hydroxy-N,N,N-trimethyl-l-propanaminium hydroxide, inner salt Structural formula:
Molecular formula: C,H.NO3
Relative molecular mass: 161.20 (calculated according to the 1995 International Table of Relative Atomic Masses) 4 Requirements
4.1 Properties
This product is a white or off-white crystalline powder; it has a slight fishy smell; it is hygroscopic. This product is very soluble in water, easily soluble in anhydrous methanol and anhydrous ethanol, slightly soluble in acetone, insoluble in chloroform, and allows agglomeration after long-term storage. 4.2 Items and indicators
Should comply with the requirements of Table 1.
Approved by the State Administration of Quality and Technical Supervision on July 12, 1999, and implemented on January 1, 2000
L-carnitine content (anhydrous).%
Specific rotation [α (anhydrous), (°) pH (5% aqueous solution)
Water, %
Residual acetone content, %
Heavy gold (Pb), mg/kg
Monumental salt (As), mg/kg
Sodium salt (Na), mg/kg
Cyanide
Fluoride (Cl-), %
Ash, %
5 Test method
GB 17787--1999
Items and indicators
97.0~103.0
-29～—32
Not detectable
The reagents used in this standard are analytically pure reagents, water is distilled water or water of corresponding purity, and unspecified solutions are aqueous solutions. The standard titration solution used in the test, unless otherwise specified, shall be prepared in accordance with the provisions of Appendix XVF of Part II of the 1995 edition of the Chinese Pharmacopoeia. The instruments and equipment are general laboratory instruments and equipment.
5.1 Identification
5.1.1 Principle
There is a secondary alcohol group in the structure of this product. When this product is melted with sulfur, an oxidation-reduction reaction will occur to produce hydrogen sulfide, which will produce black spots when it meets lead acetate test paper.
5.1.2 Reagents and solutions
a) 2% sulfur in carbon disulfide solution;
b) Glycerol;
c) Lead acetate test paper: Take a filter paper strip and dip it into the lead acetate test solution. After it is soaked, take it out and dry it at 100°C to obtain the product; d) Lead acetate test solution: Take 10g of lead acetate (HG/T3-974), add freshly boiled cold water to dissolve it, add glacial acetic acid (GB/T676) to clarify the solution, and then add freshly boiled cold water to make it 100mL to obtain the product. 5.1.3 Identification method
Take about 50mg of this product and put it in a small test tube, add a drop of 2% sulfur in carbon disulfide solution, mix it, heat it for a while, cover the dry test tube with lead acetate test paper, and suspend the test tube in a glycerol bath preheated to about 170°C. After 3min~4min, black spots will appear on the paper. 5.2 Determination of content
5.2.1 Principle
Use glacial acetic acid as solvent, crystal violet as indicator, and 0.1 mol/L perchloric acid solution as standard solution to titrate the basic nitrogen in the structure of this product. 5.2.2 Reagents and solutions
a) Glacial acetic acid (GB/T676);
b) Crystal violet indicator solution: 0.5% glacial acetic acid solution; c) Pernitrogen acid standard titration solution: 0.1 mol/L perfluoric acid glacial acetic acid standard solution. 5.2.3 Determination method
Take about 0.1g of this product, weigh it accurately, add 20mL of glacial acetic acid to dissolve it, add one drop of crystal violet indicator solution, and titrate with perchloric acid solution (0.1 mol/L) until the solution shows pure blue, and correct the titration result with a blank test. 31
5.2.4 Expression of analysis results
GB 177871999
The content of carnitine (C,HisNO) X, expressed as mass percentage, is calculated according to formula (1): X, =-V:x0.161 2 × 100
m,(1 -- X,)
Wherein: Vi
the volume of perchloric acid standard solution consumed by titrating the test solution, mL; -the volume of perchloric acid standard solution consumed by titrating the blank solution, mL; V
C--the concentration of perchloric acid standard solution, mol/L; m
-the mass of the sample·g;
X-the percentage of water in the sample, %; 0. 161 2-
The mass of L-carnitine expressed in grams equivalent to 1.00ml. of standard perchloric acid titration solution [c(HCIO,)=1.00mol/L].
5.2.5 Allowable difference
The arithmetic mean of the parallel determination results is taken as the determination result, and the relative difference of the parallel determination results is not greater than 0.3%. 5.3 Determination of specific rotation
5.3.1 Determination method
Take this product, accurately weigh it, dissolve it in water and quantitatively dilute it to make a solution containing about 100mg per milliliter, and determine and calculate it according to the specific rotation determination method of Appendix VE of Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.3.2 Allowable difference
The arithmetic mean of the parallel determination results is taken as the determination result, and the absolute difference of the parallel determination results is not greater than 0.2°. 5.4 Determination of pH
5.4.1 Determination method
Take 0.5g of this product, add 10mL of water to dissolve it, and use a glass electrode as the indicator electrode to measure it with an acidometer. 5.4.2 Expression of analysis results
Read the acidometer three times in the same way and take the average of the three measurements. 5.4.3 Allowable difference
The absolute difference of the three measurement results shall not exceed 0.1.5.5 Moisture
5.5.1 Determination method
Take this product and measure it according to the first method of moisture determination method in Appendix M of Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.5.2 Allowable difference
Take the arithmetic mean of the parallel measurement results as the measurement result, and the absolute difference of the parallel measurement results shall not exceed 0.2%. 5.6 Residual acetone content
5.6.1 Reagents and instruments
a) Acetone (GB/T 686);
b) Gas chromatograph.
5.6.2 Determination method
System suitability test: Use a 0.25 mm to 0.18mm styrene and divinylbenzene copolymer-102 is used as the stationary phase, the column temperature is 130℃, and the FID detector is used for detection. The theoretical plate number calculated according to the acetone peak shall not be less than 1000. Preparation of a reference solution: Take about 0.3g of acetone, accurately weigh it, place it in a 100mL volumetric flask, dissolve it with water and dilute it to the scale, shake it well, and you have it.
Preparation of the test solution: Take about 1g of the sample, accurately weigh it, place it in a 10mL volumetric flask, dissolve it with water and dilute it to the scale, shake it well, and you have it.
Determination method: Take 4μuL of the reference solution and 4μL of the test solution and inject them three times in succession respectively. Take the average value of the three calculations as the result. The acetone content of the test sample shall not exceed 0.1%. 5.6.3 Expression of analysis results
GB 17787-1999
The amount of residual acetone X expressed as a mass percentage: Calculate according to formula (2), (3) and (4): X (%) =
Wherein: A,——-peak area of the test sample in the chromatogram; A2—peak area of the reference substance in the chromatogram; m2
-injection volume of the test sample, g;
-weighed sample volume of the test sample, 8;
ma-,—weighed sample volume of the reference substance, g;
V, dilution volume of the test sample solution, mL; V4--dilution volume of the reference substance solution, ml; Vs--injection volume of the test sample solution, uL; V. —injection volume of the reference substance solution, uL; f-correction factor.
ma × Vs
5.6.4 Allowable difference The absolute difference of the parallel determination results shall not exceed 0.02%. 5.7 Determination of heavy metals
(3)
·(4)
Take 1.0g of this product, add 23ml of water and dissolve it with 2mL of acetate buffer (pH3.5), as the test solution, and determine it according to the test method for heavy metal limits in food additives in GB/T8451. 5.8 Determination of arsenic
Take 1.0g of this product, add 23ml of water. After dissolving, add 5mL of concentrated hydrochloric acid as the test solution, and determine it according to the arsenic spot method of GB/T8450.
Preparation of standard color spot
Use a pipette to transfer 2mL of arsenic standard solution [1mL solution contains 1μg arsenic (As)], place it in the wide-mouth bottle of the arsenic analyzer, and treat it in the same way as the test sample.
5.9 Determination of Sodium
5.9.1 Preparation of Standard Sodium Chloride Solution: Prepare in accordance with the provisions of Appendix VIA Chloride Test Method in Part II of the 1995 Edition of the Chinese Pharmacopoeia.
5.9.2 Determination Method
Take two portions of this product, 0.1g each, and place them in 50mL volumetric flasks respectively. After dissolving in 10mL of water, dilute to scale with water in one flask and shake well as the test solution; add 15ml of standard sodium chloride solution to the other flask and dilute to scale with water and shake well as the reference solution. The following is determined according to the impurity test method in Appendix VD Atomic Absorption Spectrophotometry in Part II of the 1995 Edition of the Chinese Pharmacopoeia. 5.10 Determination of Cyanide
Take 1.0g of this product and determine according to the first method of cyanide test method in Appendix F of Part II of the 1995 Edition of the Chinese Pharmacopoeia. 5.11 Determination of chloride
Take 0.5g of this product, add 50mL of water to dissolve, filter, take 1mL of the filtrate, and determine it according to the nitride test method in Appendix VA of Part II of the 1995 edition of the Chinese Pharmacopoeia, and compare it with the control solution made of 4.0mL of standard sodium chloride solution. 5.12 Determination of ash
5.12.1 Reagents
Sulfuric acid (GB/T625).
5.12.2 Determination method
GB 17787—1999
Take 1.0g of this product, and determine it according to the ignition residue test method in Appendix N of Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.12.3 Expression of analysis results
Ash content X expressed as mass percentage is calculated according to formula (5): X, = ms = me × 100
Where: ms is the total mass of crucible and residue, gm. Mass.·
Sample mass, g. www.bzxz.net
6 Inspection rules
(5)
6.1 The quality supervision and inspection department of the manufacturer shall conduct a full inspection of each batch of products according to the items specified in this standard. The manufacturer shall ensure that all L-carnitine shipped from the factory meets the requirements of the standard, and each product shall be accompanied by a product certificate. 6.2 The user may conduct quality inspection on the received products according to this standard. 6.3 Sampling method
Select samples according to the following sampling principles. If the number of bags in each batch is less than 3 bags, sample each bag; if the number of bags in each batch is between 4 and 300 bags, sample the number of bags indicated by √N+1; if the number of bags in each batch is more than 300 bags, sample the number of bags indicated by VN/2+1. From the selected number of bags, use the sampling tool to extend into three quarters of each bag to take samples, and quickly mix the taken samples. Use the quartering method to reduce the amount to three times the amount required for full inspection of each batch, and pack them in three clean, dry, wide-mouth bottles with ground mouths. After sealing, stick labels, indicate the product name, production date, batch number, manufacturer name, sampling date and sampler name, and send them to the laboratory for analysis. 6.4 If one of the indicators in the test results does not meet the requirements of this standard, the number of samples should be doubled, and re-sampled for re-inspection. If one of the indicators in the re-inspection results does not meet the requirements of this standard, the entire batch of products will be unqualified. 6.5 If the supply and demand parties have any objection to the product quality, the two parties may negotiate and select an arbitration unit to conduct arbitration in accordance with this standard. 7 Marking, packaging, transportation, storage
7.1 Marking
The packaging should have firm and clear markings. The content includes: product health license number, standard number, product name (marked with "food additives"), batch number, production date, net content of the product, shelf life, trademark, manufacturer name, factory address and storage conditions, etc. 7.2 Packaging
The inner packaging uses a plastic bag that meets the requirements of the Food Hygiene Law. A bag of silica gel desiccant is placed in the interlayer. The two layers are tied tightly with binding ropes, or sealed with other equivalent methods. The outer packaging uses an iron barrel and is sealed with a cover. Its performance and inspection methods should comply with relevant regulations. The net content of each barrel is 25kg (negative deviation shall not exceed 1%), 10kg, 5kg, 2kg (negative deviation of the latter three net contents shall not exceed 1.5%) or according to user requirements.
7.3 Transportation
During transportation, this product should be covered to prevent rain and moisture. It should not be mixed or transported with toxic, harmful or other polluting items. 7.4 Storage
This product should be stored in a dry place to prevent rain, moisture and heat. It should not be stored together with toxic and harmful items. The shelf life of the product is two years from the date of production.Treat the sample in the same way.
5.9 Determination of Sodium
5.9.1 Preparation of Standard Sodium Chloride Solution: Prepare in accordance with the provisions of Appendix VIA Chloride Test Method in Part II of the 1995 edition of the Chinese Pharmacopoeia.
5.9.2 Determination Method
Take two portions of this product, 0.1g each, and place them in 50mL volumetric flasks. After dissolving each portion with 10mL of water, add water to one flask to dilute to the mark, shake well as the test solution; add 15ml of standard sodium chloride solution to the other flask, dilute to the mark with water, shake well as the reference solution. The following is determined according to the impurity test method in Appendix VD Atomic Absorption Spectrophotometry in Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.10 Determination of Cyanide
Take 1.0g of this product and determine according to the first method of Cyanide Test Method in Appendix F of Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.11 Determination of chloride
Take 0.5g of this product, add 50mL of water to dissolve, filter, take 1mL of the filtrate, and determine it according to the nitride test method in Appendix VA of Part II of the 1995 edition of the Chinese Pharmacopoeia, and compare it with the control solution made of 4.0mL of standard sodium chloride solution. 5.12 Determination of ash
5.12.1 Reagents
Sulfuric acid (GB/T625).
5.12.2 Determination method
GB 17787—1999
Take 1.0g of this product, and determine it according to the ignition residue test method in Appendix N of Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.12.3 Expression of analysis results
Ash content X expressed as mass percentage is calculated according to formula (5): X, = ms = me × 100
Where: ms is the total mass of crucible and residue, gm. Mass.·
Sample mass, g.
6 Inspection rules
(5)
6.1 The quality supervision and inspection department of the manufacturer shall conduct a full inspection of each batch of products according to the items specified in this standard. The manufacturer shall ensure that all L-carnitine shipped from the factory meets the requirements of the standard, and each product shall be accompanied by a product certificate. 6.2 The user may conduct quality inspection on the received products according to this standard. 6.3 Sampling method
Select samples according to the following sampling principles. If the number of bags in each batch is less than 3 bags, sample each bag; if the number of bags in each batch is between 4 and 300 bags, sample the number of bags indicated by √N+1; if the number of bags in each batch is more than 300 bags, sample the number of bags indicated by VN/2+1. From the selected number of bags, use the sampling tool to extend into three quarters of each bag to take samples, and quickly mix the taken samples. Use the quartering method to reduce the amount to three times the amount required for full inspection of each batch, and pack them in three clean, dry, wide-mouth bottles with ground mouths. After sealing, stick labels, indicate the product name, production date, batch number, manufacturer name, sampling date and sampler name, and send them to the laboratory for analysis. 6.4 If one of the indicators in the test results does not meet the requirements of this standard, the number of samples should be doubled, and re-sampled for re-inspection. If one of the indicators in the re-inspection results does not meet the requirements of this standard, the entire batch of products will be unqualified. 6.5 If the supply and demand parties have any objection to the product quality, the two parties may negotiate and select an arbitration unit to conduct arbitration in accordance with this standard. 7 Marking, packaging, transportation, storage
7.1 Marking
The packaging should have firm and clear markings. The content includes: product health license number, standard number, product name (marked with "food additives"), batch number, production date, net content of the product, shelf life, trademark, manufacturer name, factory address and storage conditions, etc. 7.2 Packaging
The inner packaging uses a plastic bag that meets the requirements of the Food Hygiene Law. A bag of silica gel desiccant is placed in the interlayer. The two layers are tied tightly with binding ropes, or sealed with other equivalent methods. The outer packaging uses an iron barrel and is sealed with a cover. Its performance and inspection methods should comply with relevant regulations. The net content of each barrel is 25kg (negative deviation shall not exceed 1%), 10kg, 5kg, 2kg (negative deviation of the latter three net contents shall not exceed 1.5%) or according to user requirements.
7.3 Transportation
During transportation, this product should be covered to prevent rain and moisture. It should not be mixed or transported with toxic, harmful or other polluting items. 7.4 Storage
This product should be stored in a dry place to prevent rain, moisture and heat. It should not be stored together with toxic and harmful items. The shelf life of the product is two years from the date of production.Treat the sample in the same way.
5.9 Determination of Sodium
5.9.1 Preparation of Standard Sodium Chloride Solution: Prepare in accordance with the provisions of Appendix VIA Chloride Test Method in Part II of the 1995 edition of the Chinese Pharmacopoeia.
5.9.2 Determination Method
Take two portions of this product, 0.1g each, and place them in 50mL volumetric flasks. After dissolving each portion with 10mL of water, add water to one flask to dilute to the mark, shake well as the test solution; add 15ml of standard sodium chloride solution to the other flask, dilute to the mark with water, shake well as the reference solution. The following is determined according to the impurity test method in Appendix VD Atomic Absorption Spectrophotometry in Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.10 Determination of Cyanide
Take 1.0g of this product and determine according to the first method of Cyanide Test Method in Appendix F of Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.11 Determination of chloride
Take 0.5g of this product, add 50mL of water to dissolve, filter, take 1mL of the filtrate, and determine it according to the nitride test method in Appendix VA of Part II of the 1995 edition of the Chinese Pharmacopoeia, and compare it with the control solution made of 4.0mL of standard sodium chloride solution. 5.12 Determination of ash
5.12.1 Reagents
Sulfuric acid (GB/T625).
5.12.2 Determination method
GB 17787—1999
Take 1.0g of this product, and determine it according to the ignition residue test method in Appendix N of Part II of the 1995 edition of the Chinese Pharmacopoeia. 5.12.3 Expression of analysis results
Ash content X expressed as mass percentage is calculated according to formula (5): X, = ms = me × 100
Where: ms is the total mass of crucible and residue, gm. Mass.·
Sample mass, g.
6 Inspection rules
(5)
6.1 The quality supervision and inspection department of the manufacturer shall conduct a full inspection of each batch of products according to the items specified in this standard. The manufacturer shall ensure that all L-carnitine shipped from the factory meets the requirements of the standard, and each product shall be accompanied by a product certificate. 6.2 The user may conduct quality inspection on the received products according to this standard. 6.3 Sampling method
Select samples according to the following sampling principles. If the number of bags in each batch is less than 3 bags, sample each bag; if the number of bags in each batch is between 4 and 300 bags, sample the number of bags indicated by √N+1; if the number of bags in each batch is more than 300 bags, sample the number of bags indicated by VN/2+1. From the selected number of bags, use the sampling tool to extend into three quarters of each bag to take samples, and quickly mix the taken samples. Use the quartering method to reduce the amount to three times the amount required for full inspection of each batch, and pack them in three clean, dry, wide-mouth bottles with ground mouths. After sealing, stick labels, indicate the product name, production date, batch number, manufacturer name, sampling date and sampler name, and send them to the laboratory for analysis. 6.4 If one of the indicators in the test results does not meet the requirements of this standard, the number of samples should be doubled, and re-sampled for re-inspection. If one of the indicators in the re-inspection results does not meet the requirements of this standard, the entire batch of products will be unqualified. 6.5 If the supply and demand parties have any objection to the product quality, the two parties may negotiate and select an arbitration unit to conduct arbitration in accordance with this standard. 7 Marking, packaging, transportation, storage
7.1 Marking
The packaging should have firm and clear markings. The content includes: product health license number, standard number, product name (marked with "food additives"), batch number, production date, net content of the product, shelf life, trademark, manufacturer name, factory address and storage conditions, etc. 7.2 Packaging
The inner packaging uses a plastic bag that meets the requirements of the Food Hygiene Law. A bag of silica gel desiccant is placed in the interlayer. The two layers are tied tightly with binding ropes, or sealed with other equivalent methods. The outer packaging uses an iron barrel and is sealed with a cover. Its performance and inspection methods should comply with relevant regulations. The net content of each barrel is 25kg (negative deviation shall not exceed 1%), 10kg, 5kg, 2kg (negative deviation of the latter three net contents shall not exceed 1.5%) or according to user requirements.
7.3 Transportation
During transportation, this product should be covered to prevent rain and moisture. It should not be mixed or transported with toxic, harmful or other polluting items. 7.4 Storage
This product should be stored in a dry place to prevent rain, moisture and heat. It should not be stored together with toxic and harmful items. The shelf life of the product is two years from the date of production.
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